It is the long range purpose of this project to study interaction and relationships between connective tissue macromolecules as a way to understand connective tissue formation and structure. The topics of present interest are: (1) the mechanism of collagen fibril formation in vitro; (2) the size and structure of early intermediates in assmebly; (3) the effect of noncollagenous molecules on collagen assembly in vitro. We have developed a reproducible in vitro assembly system and shown that collagen fibril formation is a multi-step process. The first step leads to an aggregate of 5-100 molecules less than 8 nm wide and more than 1500 nm long. This aggregate grows in length and may reorganize to form a D-periodic thin filament. The filaments then assemble laterally to form native collagen fibrils.